Bacterial infection of CNS Flashcards
what are the 4 major symptoms of meningitis?
- headache
- stiff neck
- fever
- photophobia
Neisseria meningitidis bacteriology
- gram negative diplococci
- facultative intracellular
- human-restricted
- encapsulated (nonencapsulated strains are nonpathogenic)
what is unique about Neisseria meningitidis?
ferments glucose and maltose (not sucrose or lactose)
growth of N. meningitidis is inhibited by
trace metals and fatty acids: chocolate agar not blood agar
how is N. meningitidis transmitted?
by airborne droplets
N. meningitidis colonize
nasopharynx (only resorvoir) –> asymptomatic carrier, common in prisons, dorms, military, family of index case
N. meningitidis spread and colonization may be enhanced by
concomitant upper respiratory viral infections
Major agents of infectious meningitis
a. Pneumococcus (this lecture)
b. Group B Strep (this lecture)
c. Meningococcus (this lecture)
d. H. influenzae (Unit 6)
e. Syphilis (Unit 1)
f. Lyme (Unit 2)
g. TB (Unit 4)
h. Listeria (Unit 6)
i. Fungi (Unit 4)
j. Enterobacteriaceae (Unit 6)
k. Pseudomonas (Unit 4)
l. Viruses (next lecture)
Neisseria meningitidis (meningococcus) a. Bacteriology
i. Gram(-) diplococci
ii. Human-restricted
iii. Encapsulated
iv. ~13 serotypes
v. Oxidase(+), catalyase(+)
vi. Ferments glucose&maltose, NOT sucrose, lactose
vii. Won’t grow on blood agar; use chocolate agar or Thayer-Martin as
appropriate
Pathogenesis of Neisseria meningitidis
i. Transmitted by
airborne droplets
ii. Neisseria meningitidis Use
IgA protease to colonize nasopharnyx (only reservoir)
iii. Infection usually resolves without symptoms
1. Controlled by IgG-enhanced complement, neutrophils
2. Lifelong immunity to controlled strain
N. meningitidis
iv. Deficiency in Complement C6-C9 predisposes to spread beyond
respiratory sys. Polysaccharide capsule (primary virulence factor) resists
phagocytosis, endotoxin LOS may cause septic shock
v. Bacteria colonize:
1. Joints: septic arthritis
2. Meninges: meningitis, fatal if untreated, may still cause brain damage with treatment
vi. Can cause epidemics of meningitis
N. meningitidis Diagnosis
i. Exam:
1. Septic arthritis:
joint pain, draw joint fluid
2. Meningitis
a. Adults: classic fever/headache/stiff neck
b. Peds (2/3 of cases): irritability, convulsions, lassitude,
fever, abdominal discomfort/vomiting
c. Both: draw CSF, admit
N. meningitidis Meningococcemia?
a. Fever and hourly-spreading rash
b. Draw blood and CSF, admit to ICU
c. Waterhouse-Friderichen syndrome: high fever, shock,
widespread purpura, DIC, thrombocytopenia, destruction of adrenal glands, 50% fatal
N. meningitidis Lab
- Septic arthritis: Gram stain, culture on chocolate agar
- Meningitis: Gram stain, culture on chocolate agar, CSF smear for Gram(-) cocci
- Meningococcemia: Gram stain, culture on chocolate agar, blood tests for DIC
- PCR tests available
N. meningitidis treatment
Treatment
i. Penicillin G, alternates ceftriaxone, cefotaxime, cefuroxime, chloramphenicol
ii. Meningococcemia: also admit to ICU, support circulation and renal function
iii. NO STEROIDS
iv. Prevention
1. Vaccine
2. Antibiotic prophylaxis for close contacts
GBS
a. Organism
i. GBS = Group B Strep =
= S. agalactiae
ii. Gram(+) cocci
iii. Beta-hemolytic
iv. Encapsulated
v. Polysaccharide toxin virulence factor
vi. Serotype-specific antibody-mediated immunity
vii. Normal vaginal flora (15-45%),
viii. May also be normal flora in GI and upper respiratory tract
ix. Very seldom causes disease in previously-healthy adults; may cause
bacteremia, cellulitis, UTI with predisposing factors
GBS Pathogenesis
i. 1-2% of neonates of GBS+ mothers develop invasive disease most common cause of
neonatal sepsis,
2 types of neonatal sepsis by GBS?
- Early disease
a. Pneumonia w/ bacteremia
b. Presents 1-7d postpartum
c. Appears to be more common in US than developing world; may be masked by other causes of neonatal death - Late disease
a. Bacteremia w/ meningitis
b. Presents 1-12wk postpartum
c. Usually Serotype 3 - Prematurity and prolonged rupture of membranes are risk factors for both
GBS disease also may be seen in geriatric patients with pre-existing major health conditions
- Diabetes
- Malignancy
- Congestive heart failure
- These rare infections seem to be becoming more common; probably both improved reporting and also population becoming older, more immunosuppressed
Two groups at risk of GBS disease
- Pregnant/neonate: more common
a. Mother develops uterine infection or UTI
b. Neonate develops pneumonia (early) or meningitis (late) - Elderly with comorbidity: less common, more lethal
Diagnosis for GBS
i. Gram stain and culture of appropriate sample (tissue biopsy, aspirate, CSF)
ii. CT/MRI for abscesses
iii. Echocardiogram for endocarditis
iv. Some antigen tests are also available for blood, urine, CSF
treatment for GBS?
- penicillin or amoxicillin
- if allergic vancomycin
- surgical intervention may be needed, primarily in the geriatirc with predispostion cases
Prevention of GBS
i. Test term-pregnant patients for GBS by swab and culture. If positive:
ii. Intrapartum (during delivery) IV administration of penicillin or amoxicillin
iii. If allergic, use clindamycin or erythromycin, but resistant strains exist
iv. Strategy has reduced early disease in US over past decade, but there are questions about the sensitivity of the culture and PCR tests.
Pneumococcus
a. Organism
i. Staph pneumoniae
ii. Gram(+), catalase(-), facultative anaerobe
iii. In culture, form diplococci in chains
iv. Pathogenic strains are encapsulated
v. The most common cause of community-acquired pneumonia, bacterial meningitis, bacteremia, and otitis media, as well as an important cause of sinusitis, septic arthritis, osteomyelitis, peritonitis, and endocarditis
vi. A major childhood pathogen worldwide with deaths from pneumonia and meningitis
Meningococci encode 3 major virulence factors:
Meningococci encode 3 major virulence factors:
- IgA Protease: cleaves IgA, reduces defense of mucus membrane
- Polysaccharide capsule (resists phagocytosis)
- Endotoxin LOS (component of Gram(-) cell wall, causes fever, shock)
If enters bloodstream: meningococcemia
Colonizes favorite sites
Joints: septic arthritis
Meninges: meningitis, fatal if untreated, still may kill (
in 2-18yr age range
Pathogenesis of meningococcemia, cont:
Ab to capsule is protective vaccine
Deficiency in late-acting complement components C6-C9 is predisposing for complications
N. meningitidis Diagnosis: Exam
1/3 cases adult, 2/3 pediatric
Septic arthritis: joint pain - draw joint fluid
Meningitis:
Adults: classic fever, headache, stiff neck, progression to coma is bad
Young children: irritability, convulsions, lassitude, fever, abdominal discomfort/vomiting
Both: draw CSF, admit
Meningococcemia:
- Fever and hourly-spreading petechial skin rash (may be hard to see on dark skin) - draw blood and CSF, admit to ICU.
- Rarely, may be present for weeks before symptoms become alarming (“chronic”).
- 5-15% develop 50%-fatal Waterhouse-Friderichen syndrome: high fever, shock, widespread purpura, disseminated intravascular coagulation (DIC), thrombocytopenia, destruction of adrenal glands.
Waterhouse-Friderichen syndrome:
high fever, shock, widespread purpura, disseminated intravascular coagulation (DIC), thrombocytopenia, destruction of adrenal glands.
Septic arthritis:
Joint fluid: Gram stain and culture on chocolate agar
Meningitis: CSF:
increased PMNs, Gram stain (~50% sensitive) and culture on chocolate agar, Gram(-) cocci in CSF smear suffice for diagnosis, alternatively, latex agglutination test for capsule polysaccharide in CSF
Meningococcemia:
Blood: Gram stain and culture on chocolate agar, set of tests for DIC
N. Meningitidis Treatment
Penicillin G unless allergic, or local history of drug resistance
Alternates: Ceftriaxone, cefotaxime, and cefuroxime; if severely allergic to penicillin, chloramphenicol
Fulminant meningococcemia: admit to ICU, support circulation and renal function
Prescribing glucocorticosteriods for the rash and arthritis would be very bad, even though they are recommended for some other types of meningitis
prevention of N. Meningitidis
Close contacts of index case get prophylactic rifampin, ceftriaxone, or ciprofloxacin (excreted efficiently into saliva)
GBS = Group B Strep =
S. agalactiae
Encapsulated Gram(+) cocci
Beta-hemolytic
Polysaccharide toxin virulence factor
Pilus-like attachment virulence factor
Serotype-specific antibody-mediated immunity
Normal vaginal flora (15-45%), transmits to neonate shortly before and during delivery
May also be normal flora in GI and upper respiratory tract
GBS Risk Group 1 of 2: Neonate
1-2% of neonates of GBS+ mothers develop invasive disease
Most common cause of neonatal sepsis
Usually Serotype 3 (of 10)
2 types: Early disease Pneumonia w/ bacteremia Presents 1-7d postpartum Prevented by intrapartum IV antibiotics Late disease Bacteremia w/ meningitis Presents 1-12wk postpartum
GBS lab
CAMP test: CAMP factor secreted by B-group strep (and Listeria) enhances activity of β-hemolysin from S. aureus
GBS lab
Hippurase/Hippurate Test: Colorimetric test for hippurase, produced by GBS, Gardnerella vaginalis, Campylobacter jejuni, Listeria monocytogenes
GBS treatment
- IV Penicillin or amoxicillin
- If allergic, vancomycin
- Surgical intervention may be needed: heart valve replacement for endocarditis, abscess removal for cellulitis, amputation for diabetic foot
Strep pneumoniae Gram(+), catalase(-), facultative anaerobe In culture, form diplococci in chains Pathogenic strains are encapsulated The most common cause of
community-acquired pneumonia, bacterial meningitis, bacteremia, and otitis media, as well as an important cause of sinusitis, septic arthritis, osteomyelitis, peritonitis, and endocarditis
Pneumococcus exam
Diseases of direct extension (Non-Invasive Disease): sinusitis, otitis media, bronchitis, pneumonia
Pneumonia causes significant morbidity and mortality (10-20%)
Patient looks ill, anxious
Predispositions: asthma, COPD, chronic bronchitis, smoking or frequent exposure to cigarette smoke
Stethoscope: can hear rales in most patients, dullness to percussion in half (Heart and Lung Sounds Audio Workshop: bronchial breath and late-inspiratory crackles)
Radiology findings
Adolescents and adults: lobar consolidation
Infants and young children: scattered parenchemyal consolidation, bronchopneumonia
Staph pneumonia
Non-invasive Disease can usually be treated based on exam, optional Gram stain
Invasive Disease:
Gram stain and culture of appropriate samples (blood, sputum, CSF, abscess aspirates or biopsies). Blood cultures usually positive.
Begin antibiotic-sensitivity testing
Urine-antigen testing is available, useful for pneumonia in young children who don’t produce enough sputum for testing.
Meningitis spinal tap findings are typical of bacterial meningitis: Elevated opening pressure Elevated WBC count and neutrophil level Elevated protein Decreased glucose Highly elevated lactic acid Gram stain and culture are positive unless antibiotic treatment began >4hrs prior to tap
Pneumococcus Prevention
Prevnar7 vaccine raises protective IgG against the capsules of the seven serotypes that most commonly caused invasive disease prior to 2000.
Universal childhood vaccination with Prevnar7 starting in 2000 knocked down levels of invasive disease 90%
Childhood cases of invasive disease caused by those serotypes essentially disappeared (more effective than anyone expected)
Rates of carriage of those serotypes dropped as herd immunity was achieved
Rates of disease caused by other serotypes of pneumococcus increased (“replacement disease”)
Pneumococcus prevention
Prevnar13 vaccine, providing coverage for the original seven plus 6 of the newly-problematic serotypes, is now available.
May be used for childhood vaccination series
May be given as a booster to those who received the Prevnar7 series
